If cell development were a dance, the genesis of beta cells would be a four-step mambo. First, embryonic stem cells turn into basic building blocks that shape the digestive system. Second, those cells start defining what eventually becomes the pancreas, a hand-sized gland that assembles hormones and digestive juices. Third, some of those cells specialize in hormone production. Finally, a select group of cells becomes the body’s exclusive manufacturers of insulin, crucial for body function and resistance to diabetes. Cells go through these four steps naturally, but researchers want to harness the process to uncap a new source of vital insulin. Engineered beta cells might be used in new treatments to replace diabetes-stricken cells.
Until now, only step one had been mimicked in the lab. But Douglas Melton’s team at Harvard reported online March 15 in Nature Chemical Biology a way to recreate step two, thanks to a molecule the researchers discovered called indolactam-V. The molecule enhanced differentiation of pancreatic progenitors that contribute to insulin-expressing cells both in vitro and in mice. The team hopes the method they used to find this molecule, known as high-content chemical screening, will yield others to complete the remaining two steps and make stem cells perform as beta cells.
Melton, a Howard Hughes investigator and the Thomas Dudley Cabot professor in the natural sciences at Harvard, is one of two scientific directors, with David Scadden, of the Harvard Stem Cell Institute. The two are also cochairs of the Department of Stem Cell and Regenerative Biology, based at HMS and the Faculty of Arts and Sciences.
